Background

Thalidomide is an immunomodulatory agent with a spectrum of activity that is only partly characterized. Originally introduced as a nonbarbiturate hypnotic, it was used to treat morning sickness, but numerous instances of severe birth defects led to its withdrawal from the market. Thalidomide has been reintroduced and used for a number of immunological and inflammatory disorders, as well as multiple myeloma and other types of cancer. Thalidomide displays anti-angiogenic and immunosuppressive activity.  It modulates various cytokines, including inhibiting release of tumor necrosis factor-alpha (TNFβ) from monocytes.

Preclinical data suggests that chronic thalidomide treatment reduces amyloid pathology and gliosis in APP23 transgenic mice by way of inhibiting expression of the Aβ-generating secretase enzyme BACE1 (see He et al., 2013). This followed prior studies reporting preclinical efficacy of thalidomide in AD mouse models (e.g. Gabbita et al., 2012; Alkam et al., 2008; Greig et al., 2004; see also further reading). This literature prompted interest in a clinical evaluation of thalidomide in Alzheimer's disease.

Findings

A 24-week trial of the effect of thalidomide and placebo on CSF and plasma biomarkers including BACE1 in patients with mild to moderate Alzheimer's disease is ongoing at Banner Sun Health Research Institute in Sun City, Arizona. As of summer 2013, 25 patients had been randomized. More than 120 potential participants refused participation (AAIC 2013). Improvement of cognition will be assessed at two years. See clinicaltrials.gov.

Clinical Trial Timeline